ESTRADIOL NEGATIVELY REGULATES SECRETOGRANIN-II AND CHROMOGRANIN-A MESSENGER-RIBONUCLEIC-ACID LEVELS IN THE FEMALE RAT PITUITARY BUT NOT IN THE ADRENAL

Estradiol (E2) effects on the pituitary and adrenal secretogranin II (SgII) and chromogranin A (CgA) proteins and mRNA levels were analyzed in the adult female rat. Animals were ovariectomized or sham-operated for 2 weeks and then daily injected with various doses of 17-beta-E2 (from 5-100-mu-g) for the following week. SgII and CgA levels were determined by Western blot analysis using two specific antisera. Messenger RNA (mRNA) levels were measured by RNA slot blot analysis using specific cDNA probes. Simultaneously, pituitary LH content and gonadotropin subunit (LH-beta, FSH-beta, alpha) mRNAs were quantified. Ovariectomy promoted a significant increase in pituitary SgII and CgA proteins (2-fold vs. sham-operated animals, P < 0.01) and a concomitant rise in their mRNA levels (2.5-fold and 4.5-fold for SgII mRNA and CgA mRNA, respectively, P < 0.01). In the same animals LH-beta, FSH-beta, and alpha-subunit mRNA levels increased by 20-, 12-, and 6-fold, respectively. Estrogen replacement resulted in a parallel decrease of CgA and LH-beta mRNA to the control values, starting from the lowest steroid dose (5-mu-g). The SgII mRNA decrease was initiated only with a higher concentration of E2 (10-mu-g), as was that of alpha-subunit mRNA; yet, the SgII mRNA level remained significantly higher than in the control pituitary, even with the highest steroid dose (P < 0.05) at variance with the alpha-mRNA level. Concerning protein concentration, the postcastration increase in CgA was fully reverted with 10-mu-g E2 while that of SgII remained unaffected, as was the pituitary LH content. In the adrenal gland, neither the ovariectomy nor the E2 therapy altered significantly the SgII or CgA protein and mRNA concentrations. We conclude that, in rats, 1) ovarian factors regulate the pituitary SgII and CgA protein and mRNA steady-state levels while such factors are inefficient in the adrenal gland, 2) CgA and LH-beta mRNAs exhibit the same sensitivity to E2 while SgII and alpha-subunit mRNAs appear less sensitive, and 3) SgII and LH pituitary contents present a similar pattern of variations when the estrogenic status of the animal is modified.